Hepatobiliary Center of The First Affiliated Hospital, Nanjing Medical University; Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.
State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing, China.
Int J Biol Sci. 2024 Oct 7;20(13):5363-5374. doi: 10.7150/ijbs.96317. eCollection 2024.
Primary liver cancer (PLC) is a primary cause of cancer-related death worldwide, and novel treatments are needed due to the limited options available for treatment and tumor heterogeneity. 66 surgically removed PLC samples were cultured using the self-developed 2:2 method, and the final success rate for organoid culture was 40.9%. Organoid performance has been evaluated using comprehensive molecular measurements, such as whole-exome and RNA sequencing, as well as anticancer drug testing. Multiple organoids and their corresponding tumor tissues contained several of the same mutations, with all pairs sharing conventional TP53 mutations. Regarding copy number variations and gene expression, significant correlations were observed between the organoids and their corresponding parental tumor tissues. Comparisons at the molecular level provided us with an assessment of organoid-to-tumor concordance, which, in combination with drug sensitivity testing provided direct guidance for treatment selection. Finally, we were able to determine an appropriate pharmacological regimen for a patient with ICC, demonstrating the clinical practicality in tailoring patient-specific drug regimens. Our study provides an organoid culture technology that can cultivate models that retain most of the molecular characteristics of tumors and can be used for drug sensitivity testing, demonstrating the broad potential application of organoid technology in precision medicine for liver cancer treatment.
原发性肝癌（PLC）是全球癌症相关死亡的主要原因，由于治疗选择有限且肿瘤异质性，需要新的治疗方法。使用自行开发的 2:2 方法培养了 66 个手术切除的 PLC 样本，类器官培养的最终成功率为 40.9%。使用综合分子测量方法（如全外显子组和 RNA 测序）以及抗癌药物测试评估类器官的性能。多个类器官及其相应的肿瘤组织包含多个相同的突变，所有对都共享常规的 TP53 突变。关于拷贝数变异和基因表达，类器官与其相应的亲本肿瘤组织之间存在显著相关性。在分子水平上的比较为我们提供了类器官与肿瘤一致性的评估，这与药物敏感性测试相结合，为治疗选择提供了直接指导。最后，我们能够为 ICC 患者确定合适的药理方案，证明了在为患者量身定制药物方案方面的临床实用性。我们的研究提供了一种类器官培养技术，可以培养保留肿瘤大部分分子特征的模型，并可用于药物敏感性测试，证明了类器官技术在肝癌治疗精准医学中的广泛应用潜力。
